(R)-4-(4-chlorobenzyl)-2-(pyrrolidin-2-ylmethyl)phthalazin-1(2H)-one | 955359-79-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (R)-4-(4-chlorobenzyl)-2-(pyrrolidin-2-ylmethyl)phthalazin-1(2H)-one
• 英文别名: 4-[(4-chlorophenyl)methyl]-2-{[(2R)-2-pyrrolidinyl]methyl}-1(2H)-phthalazinone；4-[(4-chlorophenyl)methyl]-2-[(2R)-2-pyrrolidinylmethyl]-1(2H)-phthalazinone；4-[(4-chlorophenyl)methyl]-2-[[(2R)-pyrrolidin-2-yl]methyl]phthalazin-1-one
• CAS: 955359-79-2
• 化学式: C₂₀H₂₀ClN₃O
• 分子量: 353.851
• InChiKey: QQYIEGRYADBWBV-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  44.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-4-(4-chlorobenzyl)-2-(pyrrolidin-2-ylmethyl)phthalazin-1(2H)-one 在 potassium carbonate 、 一水合肼 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 丁酮 为溶剂， 反应 116.25h， 生成 (R)-N-(2-(2-((4-(4-chlorobenzyl)-1-oxophthalazin-2(1H)-yl)methyl)pyrrolidin-1-yl)ethyl)butyramide trifluoroacetate salt
  参考文献：
  名称：

  Design of Phthalazinone Amide Histamine H₁ Receptor Antagonists for Use in Rhinitis

  摘要：

  The synthesis of potent amide-containing phthalazinone H-1 histamine receptor antagonists is described. Three analogues 3e, 3g, and 9g were equipotent with azelastine and were longer-acting in vitro. Amide 3g had low oral bioavailability, low brain-penetration, high metabolic clearance, and long duration of action in vivo, and it was suitable for once-daily dosing intranasally, with a predicted dose for humans of approximately 0.5 mg per day.

  DOI：

  10.1021/acsmedchemlett.7b00112
• 作为产物：
  描述：

  苯酐 在 盐酸 、 偶氮二甲酸二异丙酯 、 sodium acetate 、 三苯基膦 、 肼 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N-甲基吡咯烷酮 、 乙醇 为溶剂， 反应 91.2h， 生成 (R)-4-(4-chlorobenzyl)-2-(pyrrolidin-2-ylmethyl)phthalazin-1(2H)-one
  参考文献：
  名称：

  WO2007/122156

  摘要：

  公开号：

文献信息

• Synthesis and pharmacological investigation of azaphthalazinone human histamine H1 receptor antagonists
  作者：Panayiotis A. Procopiou、Christopher Browning、Paul M. Gore、Sean M. Lynn、Stephen A. Richards、Robert J. Slack、Steven L. Sollis

  DOI：10.1016/j.bmc.2012.08.032

  日期：2012.10

  synthesised by stereoselective routes starting from the appropriate pyridine/pyrazine dicarboxylic acids by activation with CDI, reaction with 4-chlorophenyl acetate ester enolate to give a β−ketoester, which was hydrolysed, and decarboxylated. The resulting ketone was condensed with hydrazine to form the azaphthalazinone core. The azaphthalazinone cores were alkylated with N-Boc-D-prolinol at N-2 by Mitsunobu

  通过适当的吡啶/吡嗪二羧酸经CDI活化，与乙酸4-氯苯酯反应从适当的吡啶/吡嗪二羧酸开始，通过立体选择路线合成了5-Aza，6-aza，7-aza和8-aza-酞嗪酮模板和5,8-diazaphthalazinone模板。酯烯醇化得到β-酮酸酯，将其水解并脱羧。将所得的酮与肼缩合以形成氮杂酞嗪酮核。通过Mitsunobu反应在N -2处用N -Boc-D-脯氨醇使氮杂萘并酮核心烷基化，脱保护，然后在吡咯烷氮上烷基化以提供目标H 1受体拮抗剂。所有四个单氮杂酞菁酮系列均对人H 1具有更高的亲和力（pK i）受体比氮卓斯汀，但不如母体非氮杂酞菁酮有效。5,8-重氮酞嗪酮与氮卓斯汀等价。效力最低的系列是7-氮杂萘并酮，而5-氮杂萘并酮的亲脂性最高。亲水性更高的系列是8-氮杂系列。吡咯烷上的N-甲基取代基被正丁基取代引起效力（pA 2）的增加和亲脂性的相应增加。在正丁基类似物（2-甲氧基乙基）中引入β-醚氧可降低H
• [EN] PHTHALAZINE AND PYRIDO [3,4-D] PYRIDAZ INE COMPOUNDS AS H1 RECEPTOR ANTAGONISTS<br/>[FR] PHTHALAZINE ET COMPOSÉS PYRIDO-[3,4-D]PYRIDAZINE COMME ANTAGONISTES DU RÉCEPTEUR H1
  申请人：GLAXO GROUP LTD

  公开号：WO2009047336A1

  公开（公告）日：2009-04-16

  The present invention relates to compounds of formula (I), and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various diseases, such as allergic rhinitis.

  本发明涉及式(I)的化合物及其盐，其制备方法，含有它们的组合物以及它们在治疗各种疾病（如过敏性鼻炎）中的用途。
• COMPOUNDS
  申请人：GORE Martin Paul

  公开号：US20080039444A1

  公开（公告）日：2008-02-14

  The present invention relates to compounds of formula (I), and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various disorders, such as allergic rhinitis.

  本发明涉及式(I)化合物及其盐，其制备过程，含有它们的组合物以及它们在治疗各种疾病（如过敏性鼻炎）中的用途。
• 2-Substituted 4-Benzylphthalazinone Derivatives as Histamine H1 and H3 Antagonists
  申请人：Gore Paul Martin

  公开号：US20090105225A1

  公开（公告）日：2009-04-23

  The present invention relates to compounds of formula (I), and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various disorders, such as allergic rhinitis.

  本发明涉及公式(I)的化合物及其盐，其制备方法，含有它们的组合物以及它们在治疗各种疾病，如过敏性鼻炎中的应用。
• PHTHALAZINE AND PYRIDO[3,4-D]PYRIDAZINE COMPOUNDS AS H1 RECEPTOR ANTAGONISTS
  申请人：Gore Paul Martin

  公开号：US20100216799A1

  公开（公告）日：2010-08-26

  The present invention relates to compounds of formula (I), and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various diseases, such as allergic rhinitis.

  本发明涉及公式（I）的化合物及其盐，其制备方法，含有它们的组合物以及它们在治疗各种疾病（例如过敏性鼻炎）中的使用。